Summary: Oral cancer affects nearly 300,000 Americans each year and is a serious health concern due to its poor prognosis and high recurrence rate. Moreover, the worldwide tobacco epidemic is leading to thousands of new cases of oral cancer being diagnosed each year. Targeting preventive strategies for those at highest risk for oral cancer due to tobacco exposure is thus a high priority. Our ultimate goal is to employ a food-based cancer preventive strategy for high-risk populations that allows excellent long-term adherence and efficacy. The oral cavity is an open microbial ecosystem that plays host to over 700 species of bacteria that form health compatible communities called biofilms. We have previously demonstrated that these biofilms are rapidly enriched for pathogenic bacteria in smokers, resulting in an early hyper-inflammatory response. Furthermore, smoking cessation reverses this pathogenic bacterial recolonization, demonstrating that smoking has a direct effect on the oral microbiome and may increase the risk for oral carcinogenic processes by disturbing normal host-bacterial interactions. Therefore, our central hypothesis is that a critical bi-directional interaction exists between oral bacteria and phytochemical-rich black raspberry food products, which ultimately results in attenuation of inflammation and amelioration of disease. The proposed Administrative Supplement is in response to PA-17-447: Validation Studies of Analytical Methods for Dietary Supplements and Natural Products. We aim to validate a UHPLC UV-Vis/QTOF MS method for quantifying urolithins and protocatechuic acid in biological specimens. Successful completion of this aim will specifically support a primary objective of U01CA188250 ?Interactive Omics: Black raspberry metabolites and the oral microbiome in smokers?. The aim is designed to examine the effect of oral bacterial communities on metabolism of BRBs in current and never smokers. The validated method will focus upon the targeted HPLC-MS/MS analysis will be used to identify known phenolics and metabolites. The validated method will be disseminated through publication and will support reproducibility in future research of putative biologically active botanical constituents, indicators of bioavailability, and of potential metabolic states.